It is planned to investigate the effects and mechanism of Dichloroacetate (DCA) therapy in diabetic animals. To evaluate the extrahepatic effects of DCA, functional hepatectomy will be performed by diverting hepatic portal vein blood flow into the inferior vena cava. In this manner, one can examine the expected accumulation of gluconeogenesis precursors in the blood and the effect of DCA on the rate of accumulation. If DCA has major extrahepatic effects, DCA treatment should significantly retard the normal release of these precursors from skeletal muscle, for example, into the blood stream. Experiments are planned to pre-treat experimental diabetic dogs with DCA. The results will be compared to control diabetic dogs receiving 154 mM NaCl. Hepatic blood flow will then be diverted, and frequent blood samples will be obtained to monitor the accumulation of lactate, pyruvate, and amino acids which are released from extrahepatic tissues. Additional measurements will be made of glucose, ketone bodies, glycerol, and of blood flow from the hind limb to allow calculation of absolute rates of production or utilization of these substrates. Amino acid measurements will examine not only alanine and glutamine (the major gluconeogenic amino acids) but all amino acids by use of an amino acid analyzer. These experiments should delineate in part the effects of DCA, in particular whether DCA has major effects on blood lactate through the activation of peripheral glucose metabolism.